GLUCOCORTICOID-REGULATED COMPARTMENTALIZATION OF CELL SURFACE-ASSOCIATED GLYCOPROTEINS IN RAT HEPATOMA-CELLS - EVIDENCE FOR AN INDEPENDENT RESPONSE THAT REQUIRES RECEPTOR FUNCTION AND DENOVO RNA-SYNTHESIS
GLUCOCORTICOID-REGULATED COMPARTMENTALIZATION OF CELL SURFACE-ASSOCIATED GLYCOPROTEINS IN RAT HEPATOMA-CELLS - EVIDENCE FOR AN INDEPENDENT RESPONSE THAT REQUIRES RECEPTOR FUNCTION AND DENOVO RNA-SYNTHESIS
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DOI：
10.1128/mcb.7.4.1508
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发表时间：
1987-04-01
影响因子：
5.3
通讯作者：
FIRESTONE, GL
中科院分区：
文献类型：
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作者：
HAFFAR, OK;VALLERGA, AK;FIRESTONE, GL
在M1.54（一种MMTV感染的大鼠肝癌组织培养细胞的克隆系）中，研究了糖皮质激素在细胞表面相关小鼠乳腺肿瘤病毒（MMTV）糖蛋白区室化中的作用。在暴露于地塞米松（一种合成糖皮质激素）的整个时间过程中，检测细胞[2- 3 H]甘露糖标记和细胞表面125 I标记的MMTV糖蛋白的表达。表面MMTV糖蛋白的翻译后定位需要6小时的激素暴露，并发生约4小时后，其在细胞内部分的初始生产。这种调节定位到细胞表面与糖皮质激素受体占用率，并受到抑制暴露于RU 38486，一个强大的拮抗剂糖皮质激素介导的反应。细胞表面免疫沉淀表明，放线菌素D，从头RNA合成的抑制剂，防止调节细胞表面病毒糖蛋白的表达，这表明新合成的细胞成分介导这一过程。细胞表面MMTV糖蛋白的定位在转录变体（CR 1）中表现正常，该变体在地塞米松存在下产生基础水平的MMTV RNA和糖蛋白前体。因此，病毒糖蛋白的调控区室化不是临界前体浓度的必然结果。两者合计，我们的研究结果表明，翻译后贩运的细胞表面注定MMTV糖蛋白导致一个独立的糖皮质激素反应，需要受体功能和从头RNA合成。
The role of glucocorticoid hormones in the compartmentalization of cell surface-associated mouse mammary tumor virus (MMTV) glycoproteins was examined in M1.54, a cloned line of MMTV-infected rat hepatoma tissue culture cells. The expression of cellular [2-3H]mannose-labeled and cell surface 125I-labeled MMTV glycoproteins was examined throughout a time course of exposure to dexamethasone, a synthetic glucocorticoid. Posttranslational localization of surface MMTV glycoproteins required 6 h of exposure to hormone and occurred approximately 4 h after their initial production in an intracellular fraction. This regulated localization to the cell surface correlated with glucocorticoid receptor occupancy and was inhibited by exposure to RU 38486, a powerful antagonist of glucocorticoid-mediated responses. Cell surface immunopreciptation demonstrated that actinomycin D, an inhibitor of de novo RNA synthesis, prevented regulated expression of cell surface viral glycoproteins, suggesting that newly synthesized cellular components mediate this process. The localization of cell surface MMTV glycoproteins appeared normal in a transcriptional variant (CR1) that produces basal level of MMTV RNA and glycoprotein precursors in the presence of dexamethasone. Thus, regulated compartmentalization of viral glycoproteins is not an obligate consequence of a critical precursor concentration. Taken together, our results suggest that posttranslational trafficking of cell surface-destined MMTV glycoproteins resulted from an independent glucocorticoid hormone response that required receptor function and de novo RNA synthesis.